Abstract
Purpose Accumulated evidence suggests that reproductive factors are related to different breast cancer subtypes, but most studies on these relationships are mainly focused on middle-aged and older patients, and it remains unclear how reproductive factors impact different subtypes of breast cancer in young women. Methods We assessed the relationships between fertility factors and luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-enriched, and triple-negative breast cancer (TNBC) subtypes in 3792 patients and 4182 controls aged 20–70 years. Data on the reproductive history of the study participants were acquired through face-to-face interviews and questionnaires. We conducted case-control comparisons among tumor subtypes based on estrogen receptor (ER), progesterone receptor (PR), and HER2 statuses using unconditional polychotomous multivariate logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs). Results Parity was inversely related to both luminal A and luminal B subtypes in young women and older women (all Ptrend < 0.05). Later age at first full-term birth was inversely related to the luminal A subtype (Ptrend < 0.05) in young women but correlated with an increased risk of the luminal A subtype (Ptrend < 0.05) in older women. Parous Chinese women 40 years old or younger who breastfed for 12 months or longer had a lower risk of luminal B and TNBC subtypes than women who never breastfed (OR = 0.55, 95% CI 0.36-0.84 and OR = 0.52, 95% CI 0.28-0.99, respectively). Conclusions Our results implied that parity exerted a strong protective effect against luminal A and luminal B subtype breast cancer in young Chinese women, and long-term breastfeeding obviously decreased the risk of luminal B and TNBC subtypes in this population.
Highlights
Breast cancer is universally accepted as a heterogeneous disease with different molecular subtypes
We examined multiplicative interaction terms generated by age at diagnosis between reproductive factors and tumor subtypes using logistic regression models and models stratified by age (≤40/>40 years of age)
The number of live births was not related to the risk of human epidermal growth factor receptor 2 (HER2)-enriched or triple-negative breast cancer (TNBC) subtypes but was significantly inversely associated with the risk of the other two subtypes
Summary
Breast cancer is universally accepted as a heterogeneous disease with different molecular subtypes. Molecular subtypes of breast cancer are defined by the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2). Many studies have shown that different subtypes of breast cancer have diverse clinicopathological features and prognoses [1,2,3]. The results of meta-analyses have suggested that fertility factors impact the etiology of breast cancer across tumor subtypes for women of diverse races in the globe [4,5,6,7]. Compared with breast cancer in older patients, BCYW usually displays different molecular subtypes that have more aggressive biological characteristics. BCYW tends to be detected in an advanced stage and carry a poor prognosis, which suggests that the pathogenesis of the disease in young patients is different from that in older patients [16,17,18]
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